The proposed continuation project will determine if sex-related differences in BALB/c mouse spleen cell responses to mitogens and alloantigens can be detected between 12 months and 2 years of age. The mice will be tested at approximately 3 month intervals. In addition, prostaglandin E levels of spleen cells in culture will be assayed at the same time periods. It is hypothesized from previous work performed in this laboratory that prostaglandin levels will rise as immune response levels decline with age, since prostaglandin E may be one of the immunosuppresant substances involved in the aging process. Also to determine the role of the sex hormones, gonadal ablations will be performed on male and female mice of the varying ages. Three months following this procedure, replacement therapy with appropriate and opposing sex hormones will be carried out. Immune responses will be measured after castration and after replacement therapy. Controls of intact and sham-operated mice, as well as mice injected with control hormone vehicle, will also be tested.